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Water-soluble CO-releasing molecules inhibit activation of donor renal dendritic cells and suppress graft rejection

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Author:
No author available
Journal Title:
Chinese Journal of Organ Transplantation
Issue:
8
DOI:
10.3760/cma.j.issn.0254-1785.2012.08.005
Key Word:
小鼠;肾移植;一氧化碳;树突细胞;移植物排斥;Mice;Kidney transplantation;Carbon monoxide;Dendritic cells;Graft rejection

Abstract: Objective To investigate the effect and underling mechanism of water-soluble CO-releasing molecules (CORM-3) on the alleviation of allograft rejection after mouse kidney transplantation.Methods A mice kidney transplantation model was established using C.FVB-Tg (Itgax-DTR/GFP)57Lan/J or C57BL/6J (H-2Kb) mice as donors,and Balb/c (H-2Kd) mice as recipients.After donor nephrectomy,kidney was preserved in UW solution which contained CORM-3 or iCORM (inactive CO-releasing molecules) for 24 h in 4℃.Recipient survival after removal of both na? ve kidneys,serum creatinine as well as graft histology was observed.In the C.FVB-Tg(ItgaxDTR/GFP) 57Lan/J donors,rDCs were acquired in vitro and selected by magnetic cell sorting (MACS) after graft nephrectomy.The expression of activation markers,CD80 and CD86,on rDC was assessed by using flow cytometry.Results The graft medium survival time was 40.5 days in the iCORM group and 70 days in the CORM-3 group respectively (P<0.05).CORM-3 preserved the graft function as shown by significantly lower serum creatinine (P<0.05; or P<0.01) and alleviated graft pathology injury.Diffuse infiltration of mononuclear cells in the interstitial tissues,moderate tubulitis and partial glomerular sclerosis were found in the iCORM graft kidney,while the CORM-3 graft kidney displayed almost normal histology.Meanwhile,CORM-3 suppressed the expression of CD80 and CD86 in donor-derived rDC.Conclusion CORM-3 can alleviate allograft rejection,prolong the graft survival,and improve kidney function in mouse kidney transplantation,probably via inhibiting rDC activation.

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